Cytokine removal on extracorporeal life support for treatment of acute endotoxemia: A randomized controlled animal study

Weerwind, Patrick W.; Veen, Frederik H. van der; Gelsomino, Sandro; Nagaraj, Naveen Gaddehosur; Parise, Orlando; Lorusso, Roberto; Gensini, Gian Franco

doi:10.1016/j.ijcard.2013.07.175

Cited by 4 publications

(2 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results suggested that reduction of H 2 O 2 by mSPAM nanoassembly gave rise to suppression of HIF1α-mediated NF-κB activation, further preventing expression of pro-inflammatory cytokines. Apart from anti-inflammatory agent treatment and extracorporeal therapy, treatment strategies are quite limited for LPS-induced endotoxemia. − MnO 2 -based nanomaterials have been widely studied due to their H 2 O 2 -scavenging properties for mitigating hypoxic levels in tumors, whereas their efficiency in regulation of LPS-induced sepsis and immune activation has not yet been studied until now. , We harnessed the H 2 O 2 -scavenging efficacy of mSPAM nanoassembly to mitigate H 2 O 2 levels in LPS-induced sepsis models.…”

mentioning

confidence: 99%

Peroxidase-Mimicking Nanoassembly Mitigates Lipopolysaccharide-Induced Endotoxemia and Cognitive Damage in the Brain by Impeding Inflammatory Signaling in Macrophages

et al. 2018

View full text Add to dashboard Cite

Oxidative stress during sepsis pathogenesis remains the most-important factor creating imbalance and dysregulation in immune-cell function, usually observed following initial infection. Hydrogen peroxide (H2O2), a potentially toxic reactive oxygen species (ROS), is excessively produced by pro-inflammatory immune cells during the initial phases of sepsis and plays a dominant role in regulating the pathways associated with systemic inflammatory immune activation. In the present study, we constructed a peroxide scavenger mannosylated polymeric albumin manganese dioxide (mSPAM) nanoassembly to catalyze the decomposition of H2O2 responsible for the hyper-activation of pro-inflammatory immune cells. In a detailed manner, we investigated the role of mSPAM nanoassembly in modulating the expression and secretion of pro-inflammatory markers elevated in bacterial lipopolysaccharide (LPS)-mediated endotoxemia during sepsis. Through a facile one-step solution-phase approach, hydrophilic bovine serum albumin reduced manganese dioxide (BM) nanoparticles were synthesized and subsequently self-assembled with cationic mannosylated disulfide cross-linked polyethylenimine (mSP) to formulate mSPAM nanoassembly. In particular, we observed that the highly stable mSPAM nanoassembly suppressed HIF1α expression by scavenging H2O2 in LPS-induced macrophage cells. Initial investigation revealed that a significant reduction of free radicals by the treatment of mSPAM nanoassembly has reduced the infiltration of neutrophils and other leukocytes in a local endotoxemia animal model. Furthermore, therapeutic studies in a systemic endotoxemia model demonstrated that mSPAM treatment reduced TNF-α and IL-6 inflammatory cytokines in serum, in turn circumventing organ damage done by the inflammatory macrophages. Interestingly, we also observed that the reduction of these inflammatory cytokines by mSPAM nanoassembly further prevented IBA-1 immuno-positive microglial cell activation in the brain and consequently improved the cognitive function of the animals. Altogether, the administration of mSPAM nanoassembly scavenged H2O2 and suppressed HIF1α expression in LPS-stimulated macrophages and thereby inhibited the progression of local and systemic inflammation as well as neuroinflammation in an LPS-induced endotoxemia model. This mSPAM nanoassembly system could serve as a potent anti-inflammatory agent, and we further anticipate its successful application in treating various inflammation-related diseases.

show abstract

mentioning

confidence: 99%

Peroxidase-Mimicking Nanoassembly Mitigates Lipopolysaccharide-Induced Endotoxemia and Cognitive Damage in the Brain by Impeding Inflammatory Signaling in Macrophages

et al. 2018

View full text Add to dashboard Cite

show abstract

“…[13,14] Polymyxin (PMX) is a cyclic cationic polypeptide antibiotic Recently, an animal study showed that the combined use of ECMO and a blood purification device was helpful in the treatment of endotoxemia. [8] In humans, a case of a septic neonate under VA ECMO support treated by PMX-DHP was reported. [10] In our case, septic shock was accompanied by cardiac dysfunction severe enough to require mechanical support by VA ECMO.…”

Section: Discussionmentioning

confidence: 99%

Use of Polymyxin B Hemoperfusion in a Patient with Septic Shock and Septic Cardiomyopathy Who Was Placed on Extracorporeal Membrane Oxygen Support

Shin

Lee

Choi

et al. 2016

Korean J Crit Care Med

View full text Add to dashboard Cite

Although shock in sepsis is usually managed successfully by conventional medical treatment, a subset of cases do not respond and may require salvage therapies such as veno-arterial extracorporeal membrane oxygenation (VA ECMO) support as well as an attempt to remove endotoxins. However, there are limited reports of attempts to remove endotoxins in patients with septic shock on VA ECMO support. We recently experienced a case of septic shock with severe myocardial injury whose hemodynamic improvement was unsatisfactory despite extracorporeal membrane oxygenation (ECMO) support. Since the cause of sepsis was acute pyelonephritis and blood cultures grew gram-negative bacilli, we additionally applied polymyxin B direct hemoperfusion (PMX-DHP) to the ECMO circuit and were able to successfully taper off vasopressors and wean off ECMO support. To the best of our knowledge, this is the first adult case in which PMX-DHP in addition to ECMO support was successfully utilized in a patient with septic shock. This case indicates that additional PMX-DHP therapy may be beneficial and technically feasible in patients with septic shock with severe myocardial injury refractory to ECMO support.

show abstract

Extracorporeal membrane oxygenation resuscitation in adult patients with refractory septic shock

Sharma

Weerwind

2014

The Journal of Thoracic and Cardiovascular Surgery

Self Cite

View full text Add to dashboard Cite

Cytokine removal on extracorporeal life support for treatment of acute endotoxemia: A randomized controlled animal study

Cited by 4 publications

References 31 publications

Peroxidase-Mimicking Nanoassembly Mitigates Lipopolysaccharide-Induced Endotoxemia and Cognitive Damage in the Brain by Impeding Inflammatory Signaling in Macrophages

Peroxidase-Mimicking Nanoassembly Mitigates Lipopolysaccharide-Induced Endotoxemia and Cognitive Damage in the Brain by Impeding Inflammatory Signaling in Macrophages

Use of Polymyxin B Hemoperfusion in a Patient with Septic Shock and Septic Cardiomyopathy Who Was Placed on Extracorporeal Membrane Oxygen Support

Extracorporeal membrane oxygenation resuscitation in adult patients with refractory septic shock

Contact Info

Product

Resources

About